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Thyroid Na+/I- symporter. Mechanism, stoichiometry, and specificity
1Department of Physiology, UCLA School of Medicine, Los Angeles, California 90095-1751, USA. sepehr@physiology.medsch.ucla.edu
The Journal of Biological Chemistry
|October 27, 1997
Summary
The rat sodium-iodide symporter (NIS) facilitates thyroid hormone uptake and exhibits electrogenic, Na+-dependent transport. Its function involves conformational changes and a 2:1 Na+/anion stoichiometry, crucial for iodide transport.
Area of Science:
- Molecular Biology
- Biophysics
- Cell Physiology
Background:
- The sodium-iodide symporter (NIS) is critical for thyroid hormone synthesis.
- Understanding NIS function is key to managing thyroid disorders.
Purpose of the Study:
- To characterize the electrophysiological and kinetic properties of the rat thyroid Na+/I- symporter (NIS).
- To elucidate the transport mechanism and stoichiometry of NIS in a heterologous expression system.
Main Methods:
- Xenopus laevis oocyte expression system
- Electrophysiology (voltage-clamp)
- Radiotracer uptake assays
- Freeze-fracture electron microscopy
Main Results:
- NIS activity is electrogenic and dependent on Na+ (apparent affinity 28 mM), with a 2:1 Na+/anion stoichiometry.
- NIS transports various anions but not perchlorate; exhibits Na+-dependent leak current and voltage-dependent charge movements.
- Turnover rates were >/=22 s-1 (Na+ uniport) and >/=36 s-1 (Na+/I- cotransport); transporter density increased ~2.5-fold.
Conclusions:
- NIS operates via an ordered simultaneous transport mechanism, with Na+ binding first.
- Conformational changes of the empty transporter contribute to observed charge movements.
- The study provides detailed kinetic and mechanistic insights into NIS function.